SAT-303 Combined Treatment of Gonadotropin Releasing Hormone Agonist and Recombinant Human Growth Hormone in Cental Precocious Puberty Patient with Underlying Leri Weill Dyschondrosteosis

Abstract

Leri-Weill dyschondrosteosis (LWD) is a rare genetic disorder of bony growth characterized by abnormal shortening of the forearms and lower legs, abnormal misalignment of the wrist (Madelung deformity), and associated short stature. As a result of shortened leg bones, LMD patients typically have short stature. Additional symptoms and severity can vary greatly from one person to another, even among members of the same family. LWD is caused by a heterozygous mutation in the short stature homeobox-containing (SHOX) gene or its regulatory elements (enhancers) located on the pseudoautosomal region 1 (PAR1) of the sex chromosomes. There are a number of reports about GH-treated SHOX-deficient patients such as LMD, idiopathic short stature, and Turner syndrome, however, in this report, we would like to introduce a rare case with underlying LWD and central precocious puberty, who was treated by combined therapy of gonadotropin releasing hormone (GnRH) agonist and recombinant human growth hormone (rhGH). A 8 years and 4 months old girl visited our clinic for short stature and breast development of Tanner stage 2. In physical examination, her height was 117 cm (<3rd percentile), weight was 22 kg (13th percentile), and BMI was 16.07 kg/m2. Her father's and mother's height was 165cm and 162 cm, respectively, and her midparental height was calculated as 157cm. There were no specific findings in family history. She showed high arched palate and disproportion of limbs. In radiologic studies, the patient showed Madelung deformity of both forearms and functional scoliosis, and her bone age was assessed to be 9 years 7 months by TW3 method. In laboratory findings, LHRH stimulation test showed a pubertal response (peak LH level: 12.4 IU/L after 30mins). Abdominopelvic ultrasonography revealed her uterus and ovary both as pubertal status and no other abnormal findings were noted. Therefore, we diagnosed her as LWD and sexual precocity, and the results of the molecular genetics test confirmed the suspicion of LWD. The combination treatment of GnRH agonist and rhGH was started to improve the final adult height for the patient with early onset pubescence and short stature. After 3 years and 7 months of treatment, her height was 146cm and additional growth gain was 29cm. Secondary sexual characteristics proceeded to Tanner stage IV in normal order, and menarche occured at 13 years old. No adverse event was observed. After 6 months of completion of treatment, her height was 150 cm which was thought to be near adult height. In conclusion, LMD patients typically have short stature and it has been known that rhGH treatment is effective for growth promotion in these patients. However, clinicians should be aware of the possibility of LWD and concominant diagnosis of precocious puberty, which could lessen the predicted adult height, and in that case, combined therapy of GnRH agonist and rhGH can be helpful to improve the final height.